کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3070551 | 1580736 | 2007 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Differentiating Alzheimer disease-associated aggregates with small molecules Differentiating Alzheimer disease-associated aggregates with small molecules](/preview/png/3070551.png)
Alzheimer disease is diagnosed postmortem by the density and spatial distribution of β-amyloid plaques and tau-bearing neurofibrillary tangles. The major protein component of each lesion adopts cross-β-sheet conformation capable of binding small molecules with submicromolar affinity. In many cases, however, Alzheimer pathology overlaps with Lewy body disease, characterized by the accumulation of a third cross-β-sheet forming protein, α-synuclein. To determine the feasibility of distinguishing tau aggregates from β-amyloid and α-synuclein aggregates with small molecule probes, a library containing 72,455 small molecules was screened for antagonists of tau-aggregate-mediated changes in Thioflavin S fluorescence, followed by secondary screens to distinguish the relative affinity for each substrate protein. Results showed that > 10-fold binding selectivity among substrates could be achieved, with molecules selective for tau aggregates containing at least three aromatic or rigid moieties connected by two rotatable bonds.
Journal: Neurobiology of Disease - Volume 28, Issue 3, December 2007, Pages 251–260